This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The lactic acidemias are heterogeneous. The project objective is to define abnormalities in metabolism, and to develop systemic approaches to therapy. Defects in pyruvate oxidation and in gluconeogenesis will be studied.